N4 component responses to pre-pulse startle stimuli in young adults: Relationship to alcohol dependence

Both physiological and behavioral studies provide evidence to suggest that deficits in frontal cortical control circuits may contribute to the risk for developing alcohol dependence. 

Event-related potential (ERP) and eye blink responses to startle and short delay prepulse-plus-startle stimuli, and psychiatric diagnoses were investigated in young adult (age 18–30years) men (n=135) and women (n=205) Mexican Americans. 

Women displayed a significant increase in the amplitude of the eye blink response to both the startle and pre-pulse-plus-startle stimuli. None of the psychiatric diagnoses were associated with differences in eye blink responses. ERP responses to the startle and prepulse-plus startle stimuli included a negative polarity wave at approximately 400ms that was of the highest amplitude in the frontal leads (N4S). 

Women were found to have significantly higher amplitude N4S responses than men. 

Participants with alcohol dependence demonstrated significantly less inhibition and more facilitation of the N4S component by the pre-pulse stimuli. 

This finding was not associated with a diagnosis of: any other drug dependence disorder (including nicotine), anxiety or affective disorder, or conduct/antisocial personality disorder. 

The present study suggests that gender and a lifetime diagnosis of alcohol dependence may selectively contribute to this frontal late wave electrophysiological response to prepulse-plus-startle stimuli.

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Request Reprint E-Mail:  cindye@scripps.edu 

A follow-up study on the quality of alcohol dependence-related information on the web

In order to evaluate the one-year evolution of web-based information on alcohol dependence, we re-assessed alcohol-related sites in July 2007 with the same evaluating tool that had been used to assess these sites in June 2006. 

Websites were assessed with a standardized form designed to rate sites on the basis of accountability, presentation, interactivity, readability, and content quality. The DISCERN scale was also used, which aimed to assist persons without content expertise in assessing the quality of written health publications. 

Scores were highly stable for all components of the form one year later (r = .77 to .95, p < .01). Analysis of variance for repeated measures showed no time effect, no interaction between time and scale, no interaction between time and group (affiliation categories), and no interaction between time, group, and scale. 

The study highlights lack of change of alcohol-dependence-related web pages across one year.


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On the Margins. Nordic Alcohol and Drug Treatment 1885-2007

During the last ten years a number of doctoral dissertations and other thorough studies of alcohol and drug treatment organisations, ideas and innovations have been published in the Nordic countries. They have been produced within historical or social science frameworks, covering various periods of the last 120 years and both alcohol and drug treatment. Most of them are written in the Scandinavian languages or Finnish and as a consequence are not accessible to an international audience. This fact was the first reason behind this book: there was a body of new Nordic research on the history of treatment that has produced new knowledge about the system and that could merit an international audience.

Another reason why the Nordic experiences may be of interest outside the region is our tradition of making comparisons. Due to their having had a long common history, with shared languages and religious and social values, it has been natural for all the Nordic countries to build up their welfare systems by looking at what their closest neighbours do. The Nordic Centre for Alcohol and Drug Research, the publisher of this book, is an eminent example of the fruitfulness of using comparative perspectives in the analysis of alcohol and drug consumption trends, policies and social reactions.

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Hazardous Drinking Concepts, Limits and Methods: Low Levels of Awareness, Knowledge and Use in the Swedish Population

To investigate the awareness and knowledge of hazardous drinking limits among the general population in Sweden and the extent to which people estimate their alcohol consumption in standard drinks to assess their level of drinking.

 A population-based study involving 6000 individuals selected from the total Swedish population was performed. Data were collected by means of a postal questionnaire. The mail survey response rate was 54.3% (n = 3200) of the net sample of 5891 persons.

With regard to drinking patterns, 10% of the respondents were abstainers, 59% were sensible drinkers and 31% were classified as hazardous drinkers. Most of the abstainers (80%), sensible drinkers (64%) and hazardous drinkers (56%) stated that they had never heard about the standard drink method. Familiarity with the hazardous drinking concept also differed between the three categories although ∼61% of sensible and hazardous drinkers expressed awareness of the concept (46% of the abstainers). Knowledge about the limits for sensible drinking was very poor. Between 94 and 97% in the three categories did not know the limit. There was a statistically significant association between having visited health care within the last 12 months and being aware of the standard drink method and the hazardous drinking concept, but not with knowing the hazardous drinking limits. Similarly, there was a significant association between having had at least one alcohol conversation in health care within the last 12 months and being aware of the standard drink method and the hazardous drinking concept, but not with knowing the hazardous drinking limits.

The results can be seen as a major challenge for the health-care system and public health authorities because they imply that a large proportion of the Swedish population does not know when alcohol consumption becomes a threat to their health. The current strategy to disseminate knowledge about sensible drinking limits to the population through the health-care system seems to have failed and new means of informing the population are warranted.      



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Request Reprint E-Mail:     preben.bendtsen@liu.se 

Alcohol Attenuates Activation in the Bilateral Anterior Insula during an Emotional Processing Task: A Pilot Study

 Alcohol acutely reduces agitation and is widely used in social situations, but the neural substrates of emotion processing during its intoxication are not well understood.

We examine whether alcohol's social stress dampening effect may be via reduced activity in the cortical systems that subserve awareness of bodily sensations, and are associated with affective distress.

Blood oxygen level-dependent activation was measured through 24 functional magnetic resonance imaging sessions in 12 healthy volunteers during an emotional face-processing task following ingestion of a moderate dose of alcohol and a placebo beverage.                    

Results revealed that bilateral anterior insula response to emotional faces was significantly attenuated following consumption of alcohol, when compared with placebo (clusters >1472 μl; corrected P < 0.05).

Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.       



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Request Reprint E-Mail:      claudiapadula@gmail.com

NIAAA Director's Report on Institute Activities to the 127th Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism - June 9, 2011

Contents

A. Legislation, Budget, and Policy	E. News Media Interactions
B. Director's Activities	F. NIAAA Program Announcement and Request for Applications Information
C. NIAAA Staff and Organization	G. NIAAA Research Programs
D. Multi-Media Products from NIAAA

Timeframe Update for Proposed Substance Use, Abuse, and Addiction Reorganization

In November of 2010, the Scientific Management Review Board (SMRB) recommended the establishment of a new institute for substance use, abuse, and addiction-related research and the dissolution of NIAAA and NIDA. After receiving the SMRB’s recommendation, I established a Task Force of scientific experts to begin a comprehensive review of the NIH substance use, abuse, and addiction research portfolio. The Task Force has met with subject matter experts from across the NIH to learn about our investments in these areas of research. During this review, it has become apparent that our portfolio in substance use, abuse, and addiction research is very complex and that the administrative steps required to implement a reorganization of this magnitude are substantial. Additionally, during the last few months, many stakeholders have requested additional input into the development of the scientific plan for the new Institute.

Based on the complexity of the portfolio, feedback from our stakeholders, and the administrative requirements to implement this reorganization, I have decided that the NIH should take additional time to review and integrate the substance use, abuse, and addiction portfolio before building the proposed institute. This will include the development of a scientific strategic plan for substance use, abuse, and addiction research and the coordination of the intramural programs of the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism. These processes will be informed by stakeholder input.

> > > >   Read More

THE WINE INFORMATION COUNCIL NEWSLETTER May 2011

In this newsletter
 
 Scientific News
 
o  Moderate Consumption of Alcoholic Beverages may Protect Men from Fatty Liver
 
o  Moderate Drinkers  Not at risk for Stomach Cancer
 
o  Pancreatic Cancer Risk increases only with Excessive Intake
of Alcoholic Beverages
 
o  Moderate Consumption of Alcoholic beverages is not Associated with Endometrial Cancer Risk
 
o  Junk Food imposes a Higher Cost to the UK Health Services (NHS) than Cigarettes &  Alcohol
 
 Feature Article
o  Moderate Wine Drinking May
Protect from Essential Tremor
 
 WIM News
 
o  Young -People Drink less in Germany
 
o  Round Table: Binge Drinking or
Art de Vivre or is There Anything in
Between?
 
 Upcoming Events
 
o  OIV Congress and General Assembly 2011, Porto, Portugal
o  Public Health International Conference 2011, London, UK

o  6th International Wine and Heart
Health Summit, Newberg, Oregon,
USA

o  Scientific Seminar: In vino sanitas?  Wine in the Focus of Medicine, Berlin, Germany


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Is the Demand for Alcoholic Beverages in Developing Countries Sensitive to Price? Evidence from China

Economic literature in developed countries suggests that demand for alcoholic beverages is sensitive to price, with an estimated price elasticity ranging from −0.38 for beer and −0.7 for liquor. 

However, few studies have been conducted in developing countries. 

We employ a large individual-level dataset in China to estimate the effects of price on alcohol demand. Using the data from China Health and Nutrition Survey for the years 1993, 1997, 2000, 2004 and 2006, we estimate two-part models of alcohol demand. 

Results show the price elasticity is virtually zero for beer and only −0.12 for liquor, which is far smaller than those derived from developed countries. Separate regressions by gender reveals the results are mainly driven by men. 

The central implication of this study is, while alcohol tax increases can raise government revenue, it alone is not an effective policy to reduce alcohol related problems in China.

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Serum urate and its relationship with alcoholic beverage intake in men and women: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort

To investigate if beer, liquor (spirits), wine and total alcohol intakes have different associations with serum urate (SU) concentrations at different ages in a cohort of young men and women. 

 

Data from 3123 participants at baseline and follow-up at 20 years were used, with balanced proportions of Caucasians and African Americans. The relationships of SU with categories of beer, liquor, wine and total alcohol intake referent to no intake were examined in sex-specific, cross-sectional analyses.

Mean age (SD) at the beginning of follow-up was 25.1 (3.6) years. Compared with non-drinkers, significant associations between higher SU concentrations and greater beer intake were observed among men and women, with more pronounced and consistent associations for women. An association between greater liquor intake and higher SU concentrations was only seen for men at the year 20 evaluation. Wine intake was not associated with SU in either sex and total alcohol was associated with higher SU concentrations in both men and women. The magnitude of the associations between alcoholic beverages intake and SU was modest (≤0.03 mg/dl/alcoholic beverage serving). 

An association between higher SU concentrations and greater beer intake was consistent and pronounced among women, but also present in men. Despite the small magnitude of the increases in SU associated with alcohol intake, clinical implications in conditions such as cardiovascular disease and gout in young adults who are moderate and heavy drinkers cannot be ruled out. 

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Request Reprint E-Mail:    ksaag@uab.edu 

Heavy drinking in early adulthood and outcomes at mid life

Heavy drinking in early adulthood among Blacks, but not Whites, has been found to be associated with more deleterious health outcomes, lower labor market success and lower educational attainment at mid-life. 

This study analysed psychosocial pathways underlying racial differences in the impact of early heavy alcohol use on occupational and educational attainment at mid-life. 

Outcomes in labor market participation, occupational prestige and educational attainment were measured in early and mid-adulthood. A mixture model was used to identify psychosocial classes that explain how race-specific differences in the relationship between drinking in early adulthood and occupational outcomes in mid-life operate. Data came from Coronary Artery Risk Development in Young Adults, a longitudinal epidemiologic study. 

Especially for Blacks, heavy drinking in early adulthood was associated with a lower probability of being employed in mid-life. Among employed persons, there was a link between heavy drinking for both Whites and Blacks and decreased occupational attainment at mid-life. We grouped individuals into three distinct distress classes based on external stressors and indicators of internally generated stress. Blacks were more likely to belong to the higher distressed classes as were heavy drinkers in early adulthood. Stratifying the data by distress class, relationships between heavy drinking, race and heavy drinking–race interactions were overall weaker than in the pooled analysis. 

Disproportionate intensification of life stresses in Blacks renders them more vulnerable to long-term effects of heavy drinking.

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Request Reprint E-Mail:  fsloan@duke.edu  

Thesis - BUILDINGING TOWARD AN INTERVENTION FOR ALCOHOL-RELATED AGGRESSION: A COGNITIVE AND BEHAVIOR TEST OF THE ATTENTION ALLOCATION MODEL"

This study provided the first direct test of the cognitive underpinnings of the attention-allocation model and attempted to replicate and extend past behavioral findings for this model as an explanation for alcohol-related aggression. 

Men were randomly assigned to a beverage (Alcohol, No-Alcohol Control) and a distraction (Moderate Distraction, No Distraction) condition. All men were provoked by a male confederate and completed a dot probe task and a laboratory aggression task without distraction or while presented with a moderate distraction task. 

Results indicated that intoxicated men whose attention was distracted displayed significantly lower levels of aggression bias and enacted significantly less physical aggression than intoxicated men whose attention was not distracted. However, aggression bias did not
account for the lower levels of alcohol-related aggression in the distraction, relative to the no distraction, condition. 

Discussion focused on how these data inform intervention programming for alcohol-related aggression.



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Does distraction reduce the alcohol–aggression relation? A cognitive and behavioral test of the attention-allocation model.

This study provided the first direct test of the cognitive underpinnings of the attention-allocation model and attempted to replicate and extend past behavioral findings for this model as an explanation for alcohol-related aggression. 

A diverse community sample (55% African American) of men (N = 159) between 21 and 35 years of age (M = 25.80) were randomly assigned to 1 of 2 beverage conditions (i.e., alcohol, no-alcohol control) and 1 of 2 distraction conditions (i.e., distraction, no-distraction). Following beverage consumption, participants were provoked via reception of electric shocks and a verbal insult from a fictitious male opponent. Participants' attention allocation to aggression words (i.e., aggression bias) and physical aggression were measured using a dot probe task and a shock-based aggression task, respectively. 

Intoxicated men whose attention was distracted displayed significantly lower levels of aggression bias and enacted significantly less physical aggression than intoxicated men whose attention was not distracted. However, aggression bias did not account for the lower levels of alcohol-related aggression in the distraction, relative to the no-distraction, condition.
 

These results replicated and extended past evidence that cognitive distraction is associated with lower levels of alcohol-related aggression in highly provoked males and provide the first known cognitive data to support the attentional processes posited by the attention-allocation model. Discussion focused on how these data inform intervention programming for alcohol-related aggression.

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Request Reprint E-Mail:  kgallagher34@gmail.com  

Northern Ireland consultation on minimum pricing

A consultation on minimum pricing and other options for Northern Ireland is currently open.

Northern Ireland's Department of Health, Social Services and Public Safety are seeking views on setting a minimum price per unit of alcohol. A press release and BBC report announced the move earlier this year.
> > > >   Read More

Report: Contributions of Alcohol Use to Teenage Pregnancy and Sexually Transmitted Infection Rates

A report from the Centre for Public Health found expected higher alcohol related hosptial admissions amongst areas with higher teenage pregancy and STI rates:

Contributions of Alcohol Use to Teenage Pregnancy and Sexually Transmitted Infection Rates

> > > >   Read More

Global burden of disease in young people aged 10—24 years: a systematic analysis

Young people aged 10—24 years represent 27% of the world's population. Although important health problems and risk factors for disease in later life emerge in these years, the contribution to the global burden of disease is unknown. We describe the global burden of disease arising in young people and the contribution of risk factors to that burden.

 

We used data from WHO's 2004 Global Burden of Disease study. Cause-specific disability-adjusted life-years (DALYs) for young people aged 10—24 years were estimated by WHO region on the basis of available data for incidence, prevalence, severity, and mortality. WHO member states were classified into low-income, middle-income, and high-income countries, and into WHO regions. We estimated DALYs attributable to specific global health risk factors using the comparative risk assessment method. DALYs were divided into years of life lost because of premature mortality (YLLs) and years lost because of disability (YLDs), and are presented for regions by sex and by 5-year age groups.

 

The total number of incident DALYs in those aged 10—24 years was about 236 million, representing 15·5% of total DALYs for all age groups. Africa had the highest rate of DALYs for this age group, which was 2·5 times greater than in high-income countries (208 vs 82 DALYs per 1000 population). Across regions, DALY rates were 12% higher in girls than in boys between 15 and 19 years (137 vs 153). Worldwide, the three main causes of YLDs for 10—24-year-olds were neuropsychiatric disorders (45%), unintentional injuries (12%), and infectious and parasitic diseases (10%). The main risk factors for incident DALYs in 10—24-year-olds were alcohol (7% of DALYs), unsafe sex (4%), iron deficiency (3%), lack of contraception (2%), and illicit drug use (2%).

 

The health of young people has been largely neglected in global public health because this age group is perceived as healthy. However, opportunities for prevention of disease and injury in this age group are not fully exploited. The findings from this study suggest that adolescent health would benefit from increased public health attention.

 

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Request Reprint E-Mail: goref@who.int   

Alcohol’s harm to others conference - Beyond the drinker

Our “Alcohol’s harm to others” conference took place on 3 June in Edinburgh. Around 100 delegates attended to hear from expert speakers and workshop leaders on the impact of excessive drinking on people other than the drinker, with a particular focus on children and young people.

Presentations can be downloaded below and the conference report will be available soon

• Prof Robin Room
• Fiona Ryan
• Louise Hill

Gospel Sobriety: Before and After

In my book-in-progress on the origins of modern recovery narrative, I look closely at the stories that came out of the post-Civil War “gospel rescue missions,” especially in New York City. These weren’t the first evangelical missions to the urban poor, of course. Specifically, they were outgrowths of similar activity during the Second Great Awakening, such as the New York City revival of 1857-58. Nor did they represent the first movement of reformed drunkards with tales to tell, emerging a couple of decades after the heyday of the Washingtonian Society. But, founded by the converts themselves in collaboration with their religious sponsors, the postbellum rescue missions combined revival, temperance, and moral reform in an unprecedented and very influential way. They moved evangelical religion in a therapeutic direction, and they acted as rebuttals to fatalistic social theory. Their growth drew social reformers to the slums to witness first-hand evidence that the far-gone drunkard and the vicious immigrant really could be changed. By the 1890s, the ex-drunkards and their patrons had produced a lively literature of conversion narratives.

The published narratives were occasionally accompanied by a fascinating before-and-after imagery. These images in particular made me realize how many historical formulations of addiction and/or recovery produce a visual rhetoric that encapsulates its particular understanding or innovation. Photographic images of the redeemed were paired with sketched recreations of what they looked like as drinkers. The effect is a transparent example of the biographical phenomenon whereby a subject’s life is constructed to fulfill the meaning of an ideologically controlling turning point–in this case, salvation. Here are a few examples.   > > > >   Read More

New York Recovery Residence Hall is the Latest in a Small But Growing Group

A residence hall for college students in recovery that is slated to open in New York City this fall is a new twist on a model that has long been used successfully in a small but growing number of colleges across the country.

Recovery residence halls are designed to help students find like-minded peers who are willing to take the clean and sober route through their college careers. The Association of Recovery Schools lists 16 colleges and universities with recovery programs.

Unlike existing recovery housing programs that are affiliated with a particular school, the New York residence, run by Hazelden, will be open to students at colleges throughout Manhattan, including Columbia University and New York University (NYU). It will be located in the trendy Tribeca neighborhood close to NYU, but will be operated in clinical partnership with the Columbia University Department of Psychiatry.   > > > >  Read More

Who Bought Whom? Revisiting “Bowman’s Compromise”

As I reported in my 1991 dissertation,(1) the fledgling Research Council on Problems of Alcohol voted to narrow its future scientific attentions to studies of alcoholism only in the autumn of 1939. Future Council research on other alcohol-related topics, including possible new studies of alcohol’s effects on the human organism or society, would henceforth be substantially de-emphasized or postponed.(2) Karl M. Bowman, chairman of the Council’s Executive Committee, suggested this shift of research focus in a September 7, 1939 letter to the Council’s Scientific Committee. Members were also sent a two-page report vigorously advocating the newly proposed policy, prepared by a Special Committee on Financial Policy.  
> > > >   Read More

Association between Val66Met polymorphism of Brain-Derived Neurotrophic Factor (BDNF) gene and a deficiency of colour vision in alcohol-dependent male patients

Brain-derived neurotrophic factor (BDNF) is a protein encoded, in humans, by BDNF gene on chromosome 11. BDNF protects adult neurons and promotes growth and differentiation during ontogenetic development but the nature and magnitude of its effects could be influenced by functional polymorphisms. 

The BDNF polymorphism Val66Met (rs6265) has been studied in the context of etiology of mental diseases including alcoholism. 

Alcoholism – a complex disorder known to be linked to several genes – has multiple manifestations, including sensory deficits such as those affecting vision. 

In the present study we examined a relationship between the Val66Met polymorphism, alcohol dependence and colour vision deficiency (CVD) in 167 alcohol-dependent men and 289 control male subjects.

Statistical analysis revealed that almost half (about 48%) of the alcohol dependent men had a CVD. In addition we found that CVD was significantly associated (P = 0.005) with the Val66Met polymorphism. The A allele containing 66Met promotes BDNF expression and this may protect humans against CVD induced by long-term excessive alcohol intake. 

The present findings indicate that alcohol-induced CVD does not depend solely on excessive alcohol consumption but is significantly influenced by genetic predisposition in the form of a specific BDNF polymorphism.



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Request Reprint E-Mail:    vibar@anatomy.usyd.edu.au 

Multidimensional alcohol craving scale and [123I] lodobenzamide SPECT as predictors of early relapse in alcohol-dependent patients

The Multidimensional Alcohol Craving Scale (MACS) and Single Photon Emission Computerized Tomography (SPECT) with 123I-iodobenzamide (123I-IBZM) can be useful tools for assessing
relapse risk in early recovery from alcohol-dependency. 

The aim of this study was to assess possible relationships between MACS score, 123I-IBZM binding and time to first heavy drinking day (TFHD) after detoxification treatment.
 
Nineteen alcohol-dependent in-patients were evaluated by MACS scale and an 123I-IBZM-SPECT, performed following alcohol detoxification treatment. At discharge, participants were advised to take naltrexone 50 mg/day for relapse prevention. TFHD was assessed over a 12-week follow up.
 
The MACS score at the beginning of the detoxification process and naltrexone treatment after detoxification were independent predictive factors for TFHD.
 
The MACS scale is a better predictor of TFHD than IBZM  binding. It is simple, non-invasive and inexpensive and appears to be
a useful instrument both for clinical practice and for research.



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Roxon approves national plan for minimum alcohol price

THE cost of some cask wine could quadruple, with Health Minister Nicola Roxon signing off on a plan to develop a nationwide minimum floor price for alcohol.

The National Preventive Health Agency has been asked to "develop the concept" as part of a plan approved by Ms Roxon but yet to be approved by her state counterparts.

The interim chief executive of the agency, Rhonda Galbally, said that while she wasn't at liberty to reveal everything in the strategic plan approved by Ms Roxon, she was prepared to confirm that it included developing the concept of a uniform alcohol floor price that would apply nationwide.

The floor price would operate separately from alcohol tax and would make it illegal for any retailer to sell alcohol below a certain price for a standard drink, allowing retailers and manufacturers to share any extra profit that accrued.

Prices of most drinks including beer would be unaffected because they were already above the likely floor price.   > > > >   Read More

The Economics of Risky Health Behaviors

Risky health behaviors such as smoking, drinking alcohol, drug use, unprotected sex, and poor diets and sedentary lifestyles (leading to obesity) are a major source of preventable deaths. 

This chapter overviews the theoretical frameworks for, and empirical evidence on, the economics of risky health behaviors. It describes traditional economic approaches emphasizing utility maximization that, under certain assumptions, result in Pareto-optimal outcomes and a limited role for policy interventions. It also details nontraditional models (e.g. involving hyperbolic time discounting or bounded rationality) that even without market imperfections can result in suboptimal outcomes for which government intervention has
greater potential to increase social welfare. 

The chapter summarizes the literature on the consequences of risky health behaviors for economic outcomes such as medical care costs, educational attainment, employment, wages, and crime. It also reviews the research on policies and strategies with the potential to modify risky health behaviors, such as taxes or
subsidies, cash incentives, restrictions on purchase and use, providing information and restricting advertising. The chapter concludes with suggestions for future research.


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Evidence for the Role of Histamine H3 Receptor in Alcohol Consumption and Alcohol Reward in Mice

Recent research suggests that histamine H3 receptor (H3R) antagonism may diminish motivational aspects of alcohol dependence. 

We studied the role of H3Rs in alcohol-related behaviors using H3R knockout (KO) mice and ligands. 

H3R KO mice consumed less alcohol than wild-type (WT) mice in a two-bottle free-choice test and in a ‘drinking in the dark’ model.
 
H3R antagonist ciproxifan suppressed and H3R agonist immepip increased alcohol drinking in C57BL/6J mice. Impairment in reward mechanisms in H3R KO mice was confirmed by the lack of alcohol-evoked conditioned place preference. 

Plasma alcohol concentrations of H3R KO and WT mice were similar. There were no marked differences in brain biogenic amine levels in H3R KO mice compared with the control animals after alcohol drinking. 

In conclusion, the findings of this study provide evidence for the role of H3R receptor in alcohol-related behaviors, especially in alcohol drinking and alcohol reward. Thus, targeting H3Rs with a specific antagonist might be a potential means to treat alcoholism in the future.


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Request Reprint E-Mail:   saara.nuutinen@helsinki.fi   

Up-Regulation of MicroRNAs in Brain of Human Alcoholics

MicroRNAs (miRNAs) are small, noncoding oligonucleotides with an important role in posttranscriptional regulation of gene expression at the level of translation and mRNA degradation. Recent studies have revealed that miRNAs play important roles in a variety of biological processes, such as cell proliferation, neuronal differentiation, developmental timing, synapse function, and neurogenesis. A single miRNA can target hundreds of mRNA transcripts for either translation repression or degradation, but the function of many human miRNAs is not known.

miRNA array analysis was performed on the prefrontal cortex of 27 individual human cases (14 alcoholics and 13 matched controls). Target genes for differentially expressed miRNAs were predicted using multiple target prediction algorithms and a consensus approach, and predicted targets were matched against differentially expressed mRNAs from the same samples. Over- and under-representation analysis was performed using hypergeometric probability and z-score tests.

Approximately 35 miRNAs were significantly up-regulated in the alcoholic group compared with controls. Target prediction showed a large degree of overlap with our published cDNA microarray data. Functional classification of the predicted target genes of the regulated miRNAs includes apoptosis, cell cycle, cell adhesion, nervous system development, and cell–cell signaling.

These data suggest that the reduced expression of genes in human alcoholic cases may be because of the up-regulated miRNAs. Cellular processes fundamental to neuronal plasticity appear to represent major targets of the suggested miRNA regulation.


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Request Reprint E-Mail:   

dayne.mayfield@mail.utexas.edu

The Effects of Gonadectomy on Age- and Sex-Typical Patterns of Ethanol Consumption in Sprague–Dawley Rats

Ethanol intake levels characteristic of adult males and females emerge postpubertally. The present set of experiments examined the consequences of prepubertal and adult gonadectomies to explore whether the presence of gonadal hormones at puberty exerts organizational influences and/or plays an activational role in age- and sex-typical patterns of ethanol consumption.

Male and female Sprague–Dawley rats were gonadectomized (GX), received sham gonadectomy (SH), or were left nonmanipulated (NM) at 1 of 2 ages, either prepubertally on postnatal day (P) 23 (early) or postpubertally in adulthood on P70 (late). Early surgery animals were tested for ethanol consumption either during adolescence (P28 to 39) or in adulthood at the same age that late surgery animals were tested (P75 to 86). Voluntary ethanol consumption was indexed using a 2-hour limited-access paradigm, with access to 2 bottles: one containing water and the other a sweetened ethanol solution.

Age of GX did not impact patterns of ethanol consumption. Removal of testicular hormones in males, regardless of age of removal, elevated consumption levels in adulthood to female-typical levels. Ovariectomy did not have notable effects on ethanol drinking in females. Ethanol intake and preference of early SH males were significantly greater than those of both late SH and NM males. Removal of the gonads prior to puberty did not influence ethanol drinking or preference during adolescence in either males or females.

These results suggest that testicular hormones play an activational role in lowering ethanol intake and preference of adult male rats. Pubertal hormones, in contrast, were found to exert little influence on ethanol drinking or preference during adolescence, although the effect of surgical manipulation itself during development was found to exert a long-lasting facilitatory effect on ethanol consumption in adulthood.



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Request Reprint E-Mail:   cvetter1@binghamton.edu 

Effects of Early Postnatal Exposure to Ethanol on Retinal Ganglion Cell Morphology and Numbers of Neurons in the Dorsolateral Geniculate in Mice

The adverse effects of fetal and early postnatal ethanol intoxication on peripheral organs and the central nervous system are well documented. Ocular defects have also been reported in about 90% of children with fetal alcohol syndrome, including microphthalmia, loss of neurons in the retinal ganglion cell (RGC) layer, optic nerve hypoplasia, and dysmyelination. However, little is known about perinatal ethanol effects on retinal cell morphology. Examination of the potential toxic effects of alcohol on the neuron architecture is important because the changes in dendritic geometry and synapse distribution directly affect the organization and functions of neural circuits. Thus, in the present study, estimations of the numbers of neurons in the ganglion cell layer and dorsolateral geniculate nucleus (dLGN), and a detailed analysis of RGC morphology were carried out in transgenic mice exposed to ethanol during the early postnatal period.

 

The study was carried out in male and female transgenic mice expressing yellow fluorescent protein (YFP) controlled by a Thy-1 (thymus cell antigen 1) regulator on a C57 background. Ethanol (3 g/kg/d) was administered to mouse pups by intragastric intubation throughout postnatal days (PDs) 3 to 20. Intubation control (IC) and untreated control (C) groups were included. Blood alcohol concentration was measured in separate groups of pups on PDs 3, 10, and 20 at 4 different time points, 1, 1.5, 2, and 3 hours after the second intubation. Numbers of neurons in the ganglion cell layer and in the dLGN were quantified on PD20 using unbiased stereological procedures. RGC morphology was imaged by confocal microscopy and analyzed using Neurolucida software.

Binge-like ethanol exposure in mice during the early postnatal period from PDs 3 to 20 altered RGC morphology and resulted in a significant decrease in the numbers of neurons in the ganglion cell layer and in the dLGN. In the alcohol exposure group, out of 13 morphological parameters examined in RGCs, soma area was significantly reduced and dendritic tortuosity significantly increased. After neonatal exposure to ethanol, a decrease in total dendritic field area and an increase in the mean branch angle were also observed. Interestingly, RGC dendrite elongation and a decrease in the spine density were observed in the IC group, as compared to both ethanol-exposed and pure control subjects. There were no significant effects of alcohol exposure on total retinal area.

Early postnatal ethanol exposure affects development of the visual system, reducing the numbers of neurons in the ganglion cell layer and in the dLGN, and altering RGCs’ morphology.



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Request Reprint E-Mail:   rfberman@ucdavis.edu